Arrowhead Pharmaceuticals (ARWR) Status Update summary

Strategic Focus and Pipeline Prioritization

• Plozasiran is prioritized for cardiometabolic diseases, with zodasiran available for partnering due to resource constraints and market competition.

• The company aims to have 20 programs in clinical studies or on the market by 2025, leveraging its TRIM RNAi platform.

• Commercial build-out will be staged, starting with ultra-rare FCS and expanding to broader indications.

• Non-dilutive capital and partnerships with Amgen, Takeda, GSK, and Royalty Pharma support late-stage and commercial activities.

• Arrowhead is advancing programs in obesity/metabolic disease, including INHBE and a new adipocyte target.

Cardiometabolic Disease Landscape and Unmet Needs

• Cardiovascular disease is the leading cause of mortality in Western societies, with obesity and diabetes increasing risk.

• Severe hypertriglyceridemia (sHTG) and FCS are linked to high risk of acute pancreatitis and cardiovascular events, with current therapies often inadequate.

• Most pancreatitis cases from chylomicronemia are due to multifactorial chylomicronemia syndrome, not FCS.

• Patients, HCPs, and payers prioritize reduction in pancreatitis, safety, infrequent dosing, and cost-effectiveness.

Genetic Validation and Therapeutic Targets

• Loss-of-function mutations in APOC3 and ANGPTL3 are associated with reduced triglycerides and lower cardiovascular risk.

• Targeting apo CIII mRNA leads to robust triglyceride reduction and decreased pancreatitis risk, outperforming traditional therapies.